Born in Townsville, Queensland, Australia, Miller grew up on a property outside the city. A tropical city where he made his own fun, riding his motorbike and quad bike, water skiing and lending a hand with fencing and cattle mustering. His parents and siblings have supported his racing career every step of the way helping reach the goal of racing in the World Championship series. Miller has been racing motorbikes and winning since he was eight years old. He started on dirt, and was the Australian Dirt Bike champion in the 65cc category in 2003. He went on to win five other Australian championships in 2005, 2006 and 2007 and numerous other local and state titles in dirt bike racing and motocross events.

2011 was his breakout year in Europe. A string of strong performances saw him win the championship in the German IDM 125cc category at the age of 16. This result won the attention of Caretta Technology's Forward Racing, an Italian race team who signed Miller to ride in the 2012 Moto3 Championship.

2012 was Miller's first year in the Moto3 World Championship. That year had Miller riding for Caretta Technology Forward Racing on a Honda chassis. Whilst the bike was not competitive it allowed Miller the opportunity to learn the circuits he would be racing in the coming years. He finished 23rd in the Moto3 Championship that year, with a best finish of 4th at the German Grand Prix, at the Sachsenring.

Miller moved to Racing Team Germany for the 2013 season, riding an FTR Honda chassis. Miller achieved thirteen points-scoring finishes during the season, and finished in seventh place in the final championship standings. His best result was a fifth-place finish – on two occasions – at the San Marino and Australian Grands Prix.

Miller moved to a factory-backed KTM motorcycle for the 2014 season, joining the Red Bull KTM Ajo squad. During the season, Miller recorded his first fastest lap, pole position, podium finish and victory during the season; in total, he won six races during the season and finished the season as runner-up – to Álex Márquez – in the championship, missing out on the title by two points.

For the 2015 season, Miller graduated into the MotoGP class, forming a part of an expanded two-rider Team LCR outfit, partnering Cal Crutchlow. Miller competed on an open specification Honda RC213V-RS motorcycle. He achieved his best finish with 11th at Catalunya. At the British Grand Prix, Miller moved up the order in the early stages, but collided with teammate Crutchlow on lap three. Miller finished the season in 19th place with 17 points.

For 2016, Miller moved to the Marc VDS Racing Team. Miller finished in 14th-place at Qatar. At Catalunya, he finished the race in a career best 10th-place. On 26 June at Assen, Jack was running strongly in the top 10 before the race was red flagged due to heavy rain. The race restarted for a 12 lap shootout, and Miller clung on to the leaders in the early laps. He was running in fourth by the end of lap 1, and inherited third when Andrea Dovizioso crashed, right behind factory Honda rider Marc Marquez. On lap 3 race leader Valentino Rossi crashed out, and a lap later Miller overtook Màrquez for the race lead. He held his nerve for the rest of the race and pulled away to claim his first premier class victory. He was the first Australian to win a MotoGP race since Casey Stoner in Australia 2012, and the first satellite rider to win a race since Toni Elias in Portugal in 2006. Miller's odds of winning going into the race were said to be 750-1, making it the biggest winning upset in MotoGP history. The rest of his season had mixed fortunes, with occasional speed being blighted by injuries, including a fractured vertebrae in Austria. He claimed three more top 10 finishes to end the year 18th in the standings.

Jack returned to the team for 2017, and although he sometimes lacked the raw pace from the previous season, he appeared to have matured and became a consistent points scorer. This fact was recognised by Honda who gave him a chance to ride their factory bike at the Suzuka 8 Hours. He recorded nine top-10 finishes during the season, with a best finish of sixth coming twice at Assen and in the wet at Misano. Despite breaking his leg whilst training before Japan, he returned for his home race in Australia and led the early laps. He finished the year 11th in the standings.

In 2018 Miller moved to Pramac Racing, now riding a Ducati, siding Danilo Petrucci, however, unlike the Italian he had to stick with a GP17. Nevertheless the Australian scored two fourth places and a pole position and finished the season in 13th position.

In 2019 Miller is now riding a current GP19 after Petrucci moved to the Ducati factory team. His new teammate is reigning Moto2 champion Francesco Bagnaia. The season started very strong for Miller in Qatar, he qualified 4th, but was forced to retire in the race due to a broken seat while battling for the lead. Miller has since finished in 2019, 4th in Argentina and has scored 4 podiums in Austin (His first podium since his 2016 Assen win), Brno, Aragon and Phillip Island.